1. Field of the Invention
The present invention relates to coupling products of cytidine-diphosphocholine and amino compounds; it relates also to a process for producing these products and their use, notably their pharmaceutical use, in particular as vaccines.
2. Description of the Prior Art
Phosphorylcholine is a simple compound which is bound in nature to lipids, polyosides and proteins. Tests have in fact shown that extracts of various stages of development of several nematodes: Nippostrongylus brasiliensis (parasite of the rat), Haemonchus contortus (parasite of the sheep), undetermined nematodes of the respiratory system of the pig and Heligmosomoides polygyrus (parasite of the mouse) contained macromolecular compounds carrying phosphorylcholine; these compounds can be demonstrated by myelomes in the mouse as possessing anti-phosphorylcholine antibody activity; for this purpose reference may be made to the article of PERY et al in European Journal of Immunology vol. 4, 1974, pp. 637-639.
The immunochemical study of the macromolecular compound bearing phosphorylcholine, obtained from Nippostrongylus brasiliensis and purified, has shown an antigene determinant common to all the extracts tested (PERY et al. 1975 b. Ann. Immunol. (Institut Pasteur) 126 C 355).
In addition, tests have shown that the injection by the intradermal route of 10 .mu.g of the above purified compound to rats, eight days before infestation, is manifested by a modification of the transit of the larvae into the lungs and by a decrease in the number of parasites dwelling in the intestine before autosterilization (PERY et al. 1975 a C.R. Acad. Sc. Paris 281 series D 203-306).
It has already been proposed to prepare conjugated products between proteins and compounds bearing phosphorylcholine groups. Thus J. Schroer and J. M. Davie in "The Journal of Immunology" Vol. 118, No. 6, 1987-94 (1977) have described the coupling of phosphorylcholine with hemocyanine and identify the fractions of antigene formed on the injection of these conjugates into guinea pigs. In the same way W. Lee, H. Cosenza and H. Kohler have described in "Nature", Vol. 247 4 January 1974, the coupling of p-diazo phenylphosphorylcholine with the tyrosine residues of proteins, such as hemocyanine or the flagellae of salmonellose. The same authors have studied the immunitary response of mice to the injection of these conjugates.
However, the syntheses of the conjugated products of the prior art, bearing phosphorylcholine groups, are complicated and the starting compounds are difficult to obtain. In addition, the coupling is done through tyrosine residues of proteins which therefore limits the generality of the coupling technique and the number of phosphorylcholine groups which can be fixed to one mole of protein.
It is an object of the invention to provide processes and products which remove these drawbacks of the prior art.